Projects in this SPORE proposal will use human tissues to understand the molecular changes important for the pathogenesis of human lung cancer, and to develop strategies for early detection of lung cancer or pre-neoplastic changes in bronchial epithelium. To economically provide valuable human tissues for these projects we will establish a Human Tissue Core. The human tissues that will be collected, processed, and stored in this Core facility include: 1) human lung cancer tissues, 2) non-neoplastic bronchial epithelium from these same individuals with lung cancer and from individuals without lung cancer, and 3) exfoliated bronchial epithelial cells (i.e., sputum, lung lavage) from individuals with increased risk of developing lung cancer. Drs. Gabrielson and Askin in the Department of Pathology are supervising an established tissue bank which includes lung tumors and bronchus removed surgically at the Johns Hopkins Medical Institutions. Because many lung cancers (especially small cell carcinomas) are not considered surgically resectable, Dr. Mark Liu of the Pulmonary Division will collect samples of tumor and associated non-neoplastic bronchial epithelium from selected individuals by bronchoscopic biopsy. In addition, collection of lung tissue will be made at the Maryland State Medical Examiner's Office from autopsies performed within 10 hours of death; this will provide tissue from individuals of varying ages with no lung cancer. Finally, because the many projects will test the ability to detect early cancer of pre-neoplasia in exfoliated cells, Dr. Tockman will provide a collection of preserved sputums from individuals with increased risk for developing lung cancers, and Dr. Liu will obtain additional material by bronchoscopy on patients with significant dysplasia. The sputum collection currently includes 4,545 sputums collected from 949 participants in the Early Lung Cancer Detection Trial for whom clinical outcome is known. Clinical data (e.g., history, response to therapy, survival) will be collected for all lung cancer patients and high-risk patients with tissue in the Core, to allow SPORE investigators to determine possible relationships between laboratory findings and clinical outcomes. This comprehensive collection of human tissue and clinical information, as well as specialized facilities and consultative expertise for diagnostic pathology and cytology, will provide a unique resource for research and promote collaboration among the various investigators of this SPORE.